Asín-Prieto Eduardo, Rodríguez-Gascón Alicia, Isla Arantxazu
Pharmacokinetics, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain; Centro de Investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
Pharmacokinetics, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain; Centro de Investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
J Infect Chemother. 2015 May;21(5):319-29. doi: 10.1016/j.jiac.2015.02.001. Epub 2015 Feb 12.
The alarming increase of resistance against multiple currently available antibiotics is leading to a rapid lose of treatment options against infectious diseases. Since the antibiotic resistance is partially due to a misuse or abuse of the antibiotics, this situation can be reverted when improving their use. One strategy is the optimization of the antimicrobial dosing regimens. In fact, inappropriate drug choice and suboptimal dosing are two major factors that should be considered because they lead to the emergence of drug resistance and consequently, poorer clinical outcomes. Pharmacokinetic/pharmacodynamic (PK/PD) analysis in combination with Monte Carlo simulation allows to optimize dosing regimens of the antibiotic agents in order to conserve their therapeutic value. Therefore, the aim of this review is to explain the basis of the PK/PD analysis and associated techniques, and provide a brief revision of the applications of PK/PD analysis from a therapeutic point-of-view. The establishment and reevaluation of clinical breakpoints is the sticking point in antibiotic therapy as the clinical use of the antibiotics depends on them. Two methodologies are described to establish the PK/PD breakpoints, which are a big part of the clinical breakpoint setting machine. Furthermore, the main subpopulations of patients with altered characteristics that can condition the PK/PD behavior (such as critically ill, elderly, pediatric or obese patients) and therefore, the outcome of the antibiotic therapy, are reviewed. Finally, some recommendations are provided from a PK/PD point of view to enhance the efficacy of prophylaxis protocols used in surgery.
目前可用的多种抗生素耐药性惊人地增加，导致针对传染病的治疗选择迅速减少。由于抗生素耐药性部分归因于抗生素的误用或滥用，改善抗生素使用情况可扭转这一局面。一种策略是优化抗菌给药方案。事实上，药物选择不当和给药剂量不足是两个主要应考虑的因素，因为它们会导致耐药性出现，进而导致临床疗效较差。药代动力学/药效学（PK/PD）分析结合蒙特卡洛模拟能够优化抗生素的给药方案，以保留其治疗价值。因此，本综述的目的是解释PK/PD分析及相关技术的基础，并从治疗角度简要回顾PK/PD分析的应用。临床断点的确定和重新评估是抗生素治疗的关键，因为抗生素的临床使用取决于这些断点。文中描述了两种确定PK/PD断点的方法，这是临床断点设置机制的重要组成部分。此外，还综述了可能影响PK/PD行为（如重症、老年、儿科或肥胖患者）从而影响抗生素治疗结果的特征改变的主要患者亚群。最后，从PK/PD角度提出了一些建议，以提高手术中预防性用药方案的疗效。
